The Skin and Gut Microbiome and Its Role in Common Dermatologic Conditions
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microorganisms Review The Skin and Gut Microbiome and Its Role in Common Dermatologic Conditions Samantha R. Ellis 1,2, Mimi Nguyen 3, Alexandra R. Vaughn 2, Manisha Notay 2, Waqas A. Burney 2,4, Simran Sandhu 3 and Raja K. Sivamani 2,4,5,6,7,* 1 PotozkinMD Skincare Center, Danville, CA 94526, USA; [email protected] 2 Department of Dermatology, University of California-Davis, Sacramento, CA 95816, USA; [email protected] (A.R.V.); [email protected] (M.N.); [email protected] (W.A.B.) 3 School of Medicine, University of California-Davis, Sacramento, CA 95817, USA; [email protected] (M.N.); [email protected] (S.S.) 4 Department of Biological Sciences, California State University, Sacramento, CA 95819, USA 5 College of Medicine, California Northstate University, Elk Grove, CA 95757, USA 6 Pacific Skin Institute, Sacramento, CA 95815, USA 7 Zen Dermatology, Sacramento, CA 95819, USA * Correspondence: [email protected] Received: 16 October 2019; Accepted: 6 November 2019; Published: 11 November 2019 Abstract: Microorganisms inhabit various areas of the body, including the gut and skin, and are important in maintaining homeostasis. Changes to the normal microflora due to genetic or environmental factors can contribute to the development of various disease states. In this review, we will discuss the relationship between the gut and skin microbiome and various dermatological diseases including acne, psoriasis, rosacea, and atopic dermatitis. In addition, we will discuss the impact of treatment on the microbiome and the role of probiotics. Keywords: gut; skin; microbiome; acne; psoriasis; rosacea; atopic dermatitis 1. The Skin Microbiome Mary Marples’s article, “Life on the human skin”, parallels the diverse ecosystems of the skin to those of our Earth [1]. Skin is likened to soil, with the human host being the Earth on which these microcosms exist. Both environments support life and exert selective pressures on these organisms, from “ ::: the desert of the forearm, [to] the tropical forest of the armpit, [and] the cool woods of the scalp”. The skin is much more than just its resident constituents—the skin is a rich ecosystem that supports diverse populations of organisms, and like all life, these microorganisms, too, are competing for their chance to survive. In this light, skin microbiome research can evolve beyond focusing on the analysis of skin inhabitants and instead foster a respect for the beautifully integrated portrait before us: the system and its ecology. By focusing on the interactions between the biological and ecological systems, one has the chance to appreciate this portrait of a unique environment and its equally unique residents coming together to form a dynamic ecosystem. The skin is comprised of three major habitats: moist, sebaceous, and dry. Sebaceous skin includes the face, chest, and back, and is a comparatively simple community, composed mainly of several species of Cutibacterium (formerly Propionibacterium), Staphylococcus bacteria, and Malassezia yeasts [2–4]. Sebum excretion appears to be the primary driving force in sebaceous microbiome development and maintenance, as sebaceous microbiomes shift dramatically around puberty when oil production increases [3]. Microorganisms 2019, 7, 550; doi:10.3390/microorganisms7110550 www.mdpi.com/journal/microorganisms Microorganisms 2019, 7, 550 2 of 19 Dry skin sites, such as the arms and legs, are also dominated by Cutibacterium acnes and Staphylococcus species, but with additional significant portions of Gammaproteobacteria and Betaproteobacteria [5]. Moist sites have more variability, with the constantly moist toe web favoring Corynebacterium growth, while the phalangeal web, which features abundant sweat glands but is generally drier, favoring Staphylococci [5]. Invaginations of the skin (e.g., hair follicles, sebaceous glands, and sweat glands) create distinct microenvironments and oxygen gradients which may promote the growth and colonization of particular microbes. For example, Cutibacteria are oxygen tolerant anaerobes, though they grow much faster in truly anaerobic environments, while Staphylococci are facultative anaerobes and grow fastest in the presence of oxygen. It is important to note that most physiological research on Staphylococcus species has been done during aerobic growth [6–11], so the effects of hypoxic or anoxic conditions on metabolism is unknown. It is apparent that the skin microbiome is important in homeostasis, partially through the maintenance of the cutaneous immune system. For example, some strains of S. epidermis have been found to enhance the innate barrier immunity and activate IL-17+ CD8 T cells to protect against infection [12]. In a study by Naik et al., mice raised in germ-free conditions exhibited a reduction in IL-17A production in the skin, that was reversible with subsequent S. epidermis colonization [13]. In addition, S. epidermis is found to induce CD8 T cell associated transcripts important in promoting tissue repair [14]. Although further research is needed to fully elucidate the workings of the cutaneous immune system, it is evident that residential microbes play an important role. 2. Gut: Local and Systemic Modulation The human gastrointestinal tract is home to several different microbial ecosystems that colonize the entire mucosal lining [15,16]. This dynamic system is influenced by genetics, diet, and several other environmental factors [17]. Nearly 10 million genes have already been identified in the gut microbiome [18], many of which are used to support the human genome in performing several important and essential functions like vitamin production, immune regulation, protection from pathogens, serum lipid modulation, and metabolism of xenobiotics and food components [19–21]. The resulting metabolites may also influence metabolism within the host, demonstrating that both the human genome and gut microbiome play a role in the metabolic pathways occurring in the human body [22,23]. The catabolic end products from the fermentation of complex carbohydrates and other undigested food components by the intestinal microbes are incorporated into the body’s short chain fatty acids (SCFAs). Therefore, any change in the gut microbiota’s composition or metabolic activity may also alter fatty acid levels [23,24]. Fermentation of prebiotics by the gut microbiota can also produce SCFAs, which may improve the function and integrity of the gut, modulate the immune system and inflammatory response, and affect lipid and glucose metabolism [25]. In fact, these byproducts may be anti-tumorigenic, as SCFAs, butyrate, acetate, and propionate, produced by the fermentation of dietary fibers by colonic microbes, have also been shown to induce apoptosis in colorectal tumor cells [26]. There is emerging evidence that free fatty acids (FFAs), in addition to serving as an important sources of energy, are also involved in several biological processes including modulation of gene expression of adipocytes, macrophages, and endothelial cells [27–30]. FFAs can also modulate cytokine and chemokine production, gene expression of adhesion molecules, and have pro-resolution and anti-inflammatory properties, thereby controlling inflammation at multiple levels [18,28,29,31–33]. Javier et al. showed that increased intestinal colonization of Akkermansia was the major predictor of serum total FFA levels, and was negatively related to the total FFA and IL-6 (a proinflammatory cytokine) levels. He also found that altered serum levels of FFAs were associated with an imbalance between Lactobacillus and Akkermansia, as well as increased serum IL-6 levels, fecal SCFA, and subclinical prevalence of metabolic alterations [24]. Gut microbiota may also convert excess proteins and amino acids into certain toxins, like indoxyl sulfate, trimethylamine N-oxide (TMAO), and p-cresyl sulfate, which may be involved in a number of Microorganisms 2019, 7, 550 3 of 19 diseases [34]. Current evidence suggests that the most effective way to improve the microbiotic profile is increasing dietary fiber, which results in an increased synthesis of SCFAs by the gut microbiome and decreased levels of certain toxic molecules [35]. In addition, supplementation with omega-3 polyunsaturated fatty acids also increases SCFA-producing bacteria [36]. Taken together, the data highlights an important relationship between human gut microbiota, its metabolism, and its related effects on overall human health. 3. Role of Diversity in the Microbiome The gut and skin microbiota are made up of trillions of microbes, derived from thousands of different strains, that live together as an intricate ecological community. These microbiota, along with their metabolic byproducts and host interactions, directly influence both normal physiology and disease processes. For instance, disruption of the normal symbiotic relationship between gut microbes and the host is associated with inflammatory bowel disease (IBD) [37,38], obesity [39], and metabolic syndrome [40]. We are still trying to understand how microbial diversity in the gut and on the skin influences health, but there is evidence that increased microbial diversity overall is associated with improved physiology and homeostasis [15]. It is important to note that diversity of microbes in the intestines varies drastically across human populations and cultures and even varies significantly within healthy individuals over time [41]. The microbiome changes considerably over the first three years after birth and is highly sensitive